serval:BIB_7DA41F41085D
Y1 receptor knockout increases nociception and prevents the anti-allodynic actions of NPY.
10.1016/j.nut.2008.06.022
18725085
000259179600017
Kuphal
K.E.
author
Solway
B.
author
Pedrazzini
T.
author
Taylor
B.K.
author
article
2008
Nutrition
0899-9007
journal
24
9
885-891
OBJECTIVE: Recent pharmacologic studies in our laboratory have suggested that the spinal neuropeptide Y (NPY) Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY. To rule out off-target effects, the present study used Y1-receptor-deficient (-/-) mice to further explore the contribution of Y1 receptors to pain modulation. METHODS AND RESULTS: Y1(-/-) mice exhibited reduced latency in the hotplate test of acute pain and a longer-lasting heat allodynia in the complete Freund's adjuvant (CFA) model of inflammatory pain. Y1 deletion did not change CFA-induced inflammation. Upon targeting the spinal NPY systems with intrathecal drug delivery, NPY reduced tactile and heat allodynia in the CFA model and the partial sciatic nerve ligation model of neuropathic pain. Importantly, we show for the first time that NPY does not exert these anti-allodynic effects in Y1(-/-) mice. Furthermore, in nerve-injured CD1 mice, concomitant injection of the potent Y1 antagonist BIBO3304 prevented the anti-allodynic actions of NPY. Neither NPY nor BIBO3304 altered performance on the Rotorod test, arguing against an indirect effect of motor function. CONCLUSION: The Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY.
Analgesics/pharmacology
Animals
Anti-Inflammatory Agents/pharmacology
Arginine/administration & dosage
Arginine/analogs & derivatives
Behavior, Animal/drug effects
Disease Models, Animal
Hot Temperature/adverse effects
Hyperalgesia/drug therapy
Hyperalgesia/genetics
Inflammation/drug therapy
Inflammation/genetics
Male
Mice
Mice, Knockout
Neuropeptide Y/genetics
Neuropeptide Y/pharmacology
Pain/drug therapy
Pain/genetics
Pain Measurement/methods
Pain Measurement/statistics & numerical data
Receptors, Neuropeptide Y/physiology
Sciatic Neuropathy/drug therapy
Sciatic Neuropathy/genetics
eng
60_published
peer-reviewed
University of Lausanne
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